Abstract

Lifespan in the nematode, C. elegans, is determined by interacting genetic pathways as well as by environmental conditions. For example, mutations in the daf-2/insulin-like signaling pathway nearly triple adult lifespan. One goal of this project is to learn why these mutants live longer. It has been shown that insulin signaling must be active in the C. elegans nervous system for normal lifespan, suggesting that neurons somehow control lifespan. One goal of this project is to identify the neurons that dictate lifespan via insulin-like signaling. A second goal of this project is to define new genes that collaborate with the insulin-like pathway. To this end, several new mutations were isolated that lengthen or shorten lifespan of long-lived insulin pathway mutants. These mutants will enable us (a) to identify the genes that are required for a long adult lifespan and (b) to identify previously unknown pathways that influence adult lifespan. Many basic biological processes are shared between nematodes and humans. Therefore, some of the genes that control lifespan in the worm may also have human versions that perform similar functions. The genes mutated in these altered-lifespan mutants are currently being mapped and cloned for molecular characterization.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000320-02
Application #
6815142
Study Section
(LN)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Hunt, Piper R; Son, Tae Gen; Wilson, Mark A et al. (2011) Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms. PLoS One 6:e21922
Iser, Wendy B; Wilson, Mark A; Wood 3rd, William H et al. (2011) Co-regulation of the DAF-16 target gene, cyp-35B1/dod-13, by HSF-1 in C. elegans dauer larvae and daf-2 insulin pathway mutants. PLoS One 6:e17369
Wilson, Mark A; Rimando, Agnes M; Wolkow, Catherine A (2008) Methoxylation enhances stilbene bioactivity in Caenorhabditis elegans. BMC Pharmacol 8:15
Iser, Wendy B; Wolkow, Catherine A (2007) DAF-2/insulin-like signaling in C. elegans modifies effects of dietary restriction and nutrient stress on aging, stress and growth. PLoS One 2:e1240
Iser, Wendy B; Gami, Minaxi S; Wolkow, Catherine A (2007) Insulin signaling in Caenorhabditis elegans regulates both endocrine-like and cell-autonomous outputs. Dev Biol 303:434-47
Zou, Sige; Sinclair, Jason; Wilson, Mark A et al. (2007) Comparative approaches to facilitate the discovery of prolongevity interventions: effects of tocopherols on lifespan of three invertebrate species. Mech Ageing Dev 128:222-6
Wolkow, Catherine A (2006) Identifying factors that promote functional aging in Caenorhabditis elegans. Exp Gerontol 41:1001-6
Lee, Garrick D; Wilson, Mark A; Zhu, Min et al. (2006) Dietary deprivation extends lifespan in Caenorhabditis elegans. Aging Cell 5:515-24
Wilson, Mark A; Shukitt-Hale, Barbara; Kalt, Wilhelmina et al. (2006) Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell 5:59-68
Wolkow, Catherine A; Iser, Wendy B (2006) Uncoupling protein homologs may provide a link between mitochondria, metabolism and lifespan. Ageing Res Rev 5:196-208

Showing the most recent 10 out of 16 publications